We will continue to work on the isolation and characterization of the intraneuronal twisted tubules which are the morphological hallmark of human senile and presenile dementia. The subunits of these structures will be characterized with respect to molecular weight, amino acid composition, peptide mapping, and ligand binding. These methods will be used to compare these subunits with those obtained from normally occurring neurofilaments and microtubules. The possible dynamics of neurons in Alzheimer's disease and in senility will be studied using animal models for neurofibrillary proliferation. Synthesis, turnover and transport of microtubule protein will be studied in these models. Attempts will be made to isolate the 100A filaments from cells with aluminum-induced neurofibrillary proliferation, and to compare these filaments to normally occurring filaments and tubules. Antitubulin antibodies and their reaction to twisted tubules and filaments will also be studied. The senile and pre-senile dementias are perhaps the greatest financial burden on society today. This research offers the possibility of opening fruitful studies of the biochemical defects in these diseases.